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Programmable artificial cells as living technology


Cardiff School of Pharmacy and Pharmaceutical Sciences

Cardiff United Kingdom Biochemistry Bioinformatics Biomedical Engineering Biophysics Chemical Engineering Computational Chemistry Molecular Biology Physical Chemistry

About the Project

PhD Studentship aligned with European Consortium Project: Artificial Cells with Distributed Cores to Decipher Protein Function

We envision a future where ‘chemical apps’ on mobile devices produce on demand valuable compounds for health and performance as well as apps for bioagent threat and disease detection. To progress toward this future vision, we will exploit the miniaturisation of lab on a chip technology and construct responsive soft architectures and metabolisms based on living cells and tissues. We will build programmable and re-configurable, (bio)chemical processes, with precision, order, and as hierarchical cellular constructs, in the same way as living systems. We will enable microscale, liquid-based, chemical compartmentalisation (cores), and inter-compartmental (core-core) communication, just as one finds in organelles, cells and tissues. In a future embodiment of this project, artificial cell technology will be used as programmable and reconfigurable matter for specific applications, including therapeutics, diagnostics and personalised medicine as well as sensing and actuation in the environments for bioremediation. The Student will benefit from integration with the ACDC pan-European research consortium and be part of a vibrant, diverse, interactive community spanning disciplines, career stages and sectors with partners in both academia and industry. The student will have opportunity to be involved in cross-site collaboration and idea generation via regular group, and sub-group, meetings. This PhD training experience will equip PhD candidates with multidisciplinary research skills that are highly sought after in academic and industry.

 

Project Description:

The field of Synthetic Biology involves the application of engineering principles to biological systems and components. Artificial cells are engineered elements made via this approach that mimic some of the essential characteristics of biological cells. Such constructs hold great promise as a new class of functional materials well suited to sophisticated and complex tasks through their potential to act in dynamic and responsive ways.

This research project builds on our existing work in the fabrication of membrane compartmentalised artificial cells that harness some of the complexity observed in biological systems [1]. As a central technology, these engineered synthetic cells provide a platform to encapsulate chemical and biochemical processes within cell-like structures that can then be programmed and orchestrated to act in dynamic and responsive ways, much like their biological counterparts. In these systems we are able to reconstitute functional water-soluble and membrane proteins, in addition to synthetic chemistries, which can be used to determine artificial cell function. In this way, we aim to develop new approaches to provide control of spatially organised chemistries, their interaction and regulation, to elicit new and useful functions, such as stimuli-responsiveness, sensing, chemical-synthesis, and smart integration of these properties. This PhD project seeks to harness the linkage of biochemical reactions across compartments, to achieve such metabolic behaviors not possible in simple one-pot systems. By exploiting biologically controlled approaches to material engineering this promises new technological capabilities with broad applications; from helping us better understand the functions of the cell and how disfunction gives rise to disease, to the development of drug discovery and characterisation platforms, new diagnostics and smart-functional-materials.

Research Environment: Cardiff is rated 5th overall in the 2014 UK Research Excellence Framework (REF). Research at Cardiff is working across disciplines to tackle major challenges facing society, the economy and the environment. You will work within a multidisciplinary team at the physical-life science interface, gaining experience across disciplines from biochemistry, single molecule techniques, membrane synthetic biology, microfluidics and molecular biology. The supervisory team have an excellent track record in supervision and publication, alongside a unique combination of expertise from which you and the project will benefit. We seek applications from enthusiastic scientists with appropriate knowledge/experience/ideas in some of the areas outlined (biochemistry|protein expression and purification|lipid membranes|biological physics|physical chemistry|chemical biology|droplets|microfabrication) with an eagerness to learn across disciplines and develop in areas new to the candidate. We do not expect prior experience in all areas. Talented and enthusiastic candidates from all backgrounds are encouraged to apply. We recognise that diversity within a team provides a greater range of experience, perspectives and ideas to draw upon when tackling problems and informing decisions.

Training and Development Opportunities: You will gain skills across the physical and life-sciences. You will develop a number of transferable research skills including experimental design, data analysis and scientific communication. This project will utilise many techniques and allow for the development of a wide array of skills. The work will take place within a multidisciplinary team of wide-ranging expertise, within which the successful candidates will play active roles and synergise with other researchers. Students will contribute to the wider European collaborative team of the Artificial Cells as Living Technology project, providing the opportunity to interact with academic and industrial partners in Italy, France and Switzerland contributing to collaborative research, network events and presenting at meetings. This is in addition to University seminars, training events and post-graduate research days. You will have the opportunity to present your findings at international conferences and publish in high impact journals. This studentship experience will result in an extremely well-rounded, interdisciplinary and highly employable individual. Future prospects look good, especially in several advanced engineering and bio-technology fields, such as bioengineering and biomedicine. Students from the supervisory labs have taken up positions in highly regarded academic institutions and companies.

Applicants should apply to the Doctor of Philosophy Pharmacy with a start date of October 2021

In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select 'I will be applying for a scholarship/grant' and specify that you are applying for advertised funding from Programmable artificial cells as living technology.

To apply - https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/pharmacy


Funding Notes

This is a fully-funded studentship which includes fees, stipend and a research and training support grant, for 3 years at UKRI rate, for home/EU students.
Self-funded international students are welcomed to apply.
Applicants should achieve 2:1 or higher in a relevant subject area of either the physical or life sciences, such as biomedical sciences, biology, pharmacy, medicine, physiology, biochemistry, chemistry, physics, engineering or related subjects. An interest in multidisciplinary research and a desire to learn across disciplines is essential.
Accepted English Language qualifications can be found here View Website

References

https://www.cardiff.ac.uk/people/view/90831-castell-oliver
[1] Baxani, D. K.et al. 2016. Bilayer networks within a hydrogel shell: A robust chassis for artificial cells and a platform for membrane studies. Angewandte Chemie International Edition 55(46), pp. 14240-14245. (10.1002/anie.201607571)
[2] Dijkman, P. M.et al. 2018. Dynamic tuneable G protein-coupled receptor monomer-dimer populations. Nature Communications 9(1), article number: 1710. (10.1038/s41467-018-03727-6)
[3] Huang, S.et al. 2015. High-throughput optical sensing of nucleic acids in a nanopore array. Nature Nanotechnology 10, pp. 986-991. (10.1038/nnano.2015.189)
[4] Hardinge, P.et al. 2020. Bioluminescent detection of isothermal DNA amplification in microfluidic generated droplets and artificial cells. Scientific Reports 10(1), article number: 21886. (10.1038/s41598-020-78996-7)

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